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- Table of Contents
Facts about Sentrin-specific protease 6.
Deconjugates SUMO1 from RXRA, resulting in transcriptional activation. Involved in chromosome alignment and spindle assembly, by regulating the kinetochore CENPH-CENPI-CENPK complicated.
Human | |
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Gene Name: | SENP6 |
Uniprot: | Q9GZR1 |
Entrez: | 26054 |
Belongs to: |
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peptidase C48 family |
EC 3.4.22.-; KIAA0797FLJ11887; Sentrin/SUMO-specific protease SENP6; sentrin-specific protease 6; SSP1KIAA0389; SUMO1/sentrin specific peptidase 6,2810017C20Rik; SUMO1/sentrin specific protease 6; SUMO-1-specific protease 1; SUSP1FLJ11355
Mass (kDA):
126.146 kDA
Human | |
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Location: | 6q14.1 |
Sequence: | 6; NC_000006.12 (75601509..75718281) |
Highly expressed in reproductive organs, such as testis, ovary and prostate.
Nucleus.
SENP6, an essential enzyme, is required for the assembly the inner kinetochore. It also regulates the level of the SUMO reducing enzyme CENPA and controls centromere identity. Many researchers still don’t know what SENP6 does. Let's take a look at the best uses this marker has in this article. You may also find it interesting to read the biochemistry for SENP6.
The SUMO deconjugating protein 6 (SENP6), which is essential for inner kinetochoral assembly and mitotic arrest, is overexpressed. The SUMO deconjugating protein is found in distinct subdomains. It may also facilitate association with a specific SUMO -modified protein.
For the assembly of inner kinetochores, SENP6 is required. SENP6 may also recruit other SUMO deconjugating proteins to the kinetochore. The exact role of SENP6 is not yet known.
SUMOs, proteins that act on polypeptide-chains to regulate their localization in cells, are called SUMOs. These proteins belong in the CE superfamily. They were first discovered in Saccharomyces cerevisiae. A second SUMO-deconjugating enzyme, SENP2, has been identified in Drosophila. The SENP7 SUMO-deconjugating enzyme is also important in inner kinetochore assembly. It is however less abundant in Xenopus levis eggs. SENP6 might act on a subset of polySUMO chains, but they both have the same function in controlling NACCAD assembly.
SENP1 & SENP6 share 80% of their sequence identity and form an homodimer. Both contain a cysteine molecule embedded in their catalytic sites. Their catalytic sites have an active spot groove and are stabilized using a Gln in the catalytic triad. A shallow tunnel allows substrate to access the catalytic site. The SENPs prefer SUMO Paralogs with specific sequences of amino acids.
Both the SUMO deconjugating enzymes SENP1 (and SENP6) play important roles in mitosis. Both are essential for the timely separation of sister chromatids at the metaphase-to-anaphase transition. They play a unique biological function and are subcellularly localized.
We have created a stable, resistant cell line that is insensitive to the SUMO -deconjugating enzymeSENP6. We used HeLa cells transfected by SENP6 siRNA. The pBABEOsTir1-9Myc Retrovirus was a gift from Andrew Holland at Johns Hopkins. To create stable cells, we also used retrovirus pLJ820.
The SENP6 Protein is an essential part the centromere. It controls the maintenance and reassemble of CENP-A chromatin onto nascent DNA. However, it is unclear whether this protein is necessary for the growth and viability of cells, or if it has other broader roles in the cell cycle.
This protein is a member of the MCM2-7 complex. It is essential for maintaining levels of CENPA in the cells' nucleosomes. SENP6 protein deficiency results in severe CENPA degradation. The protein could also play a part in maintaining the CENP6 nucleosomes. It is possible that SENP6 is required to assembly CENP-A.
The SENP6 protein is essential for maintaining the centromere complex at its hypo-SUMOylated status. It is essential for maintaining the complex architecture. Stable transmission is guaranteed by the underlying SUMOcycle. This complex is maintained by SENP6 protein. It is essential for the formation centromeres in addition to the CENPA protein.
The SENP6 marker provides a convenient and fast way to determine the level of CENP-A in the cell. The highly sensitive Picokine(tm) ELISA platform provides high sensitivity, up to the picogram level. The ELISA test kit is approved for a variety if samples. On request, validation images are available. The Supervision polymer-based secondary antibody significantly reduces the time required for IHC and saves up to 30 minutes. Picoband ELISA technology was developed using insights from immunogen design. It is supported by Sanbio as a BeNeLux distributor.
A new study reveals that SENP6, a marker that regulates chromosome malalignments in human cells, has been found to be responsible. In this study, we tested a serum containing serine protease inhibitor SENP6 to detect misaligned chromosomes. We found that SENP6-deficient cells had lower CENP-I and CENP–F levels on kinetochores. SENP6-deficient cells had dramatically decreased protein levels.
In SENP6-depleted cells, we found that the kinetochore protein Hec1 showed a significant reduction. Hec1 can be recruited to kinetochores at the end of the G2-phase of cell differentiation. Thus, we hypothesized that an inadequate load of Hec1 could contribute to the defects. This is consistent to previous reports showing that SENP6 regulates misalignment of chromosomes.
This study shows SENP6 to be a key player in NACCAD assembly control. SENP7 had a similar activity but was less prevalent in mammalian tissue-culture cells. We believe that these proteins act on different subsets or poly-SUMO chains. This work suggests that SENP6 may regulate chromosome misalignment and may be more important for the regulation of chromosome misalignment than SENP7.
SENP6 protein expression was observed in HeLa cell lines transfected by SENP6 siRNA. 40 uM of monastrol were added to the culture media 48 hours after transfection. After shaking off the medium, the mitotic cells were collected and washed three more times with ice-cold DME. After centrifugation, the cells were plated in 6-cm dishes with or without 2 uM ZM447439 (Tocris Bioscience).
CENPB is a protein necessary for de-novo centromere formation. This protein is essential for maintaining centromere identities in human cells. CENP-B is responsible for maintaining centromere identity in cells lacking CENP-A. It also contributes to stability of centromeres through recruitment of CENP-A via the Mis18 complex. Other centromere components could also be important for centromere identities.
The conserved centromere-specific histone H3 variant plays an essential role in centromere identity and functions as a key epigenetic mark. It was found in human scleroderma patients, and it has been characterized as an human autoantigen. It copurifies with nucleosomes. Histones. Chromin. CENP A nucleosomes are interspersed at the centromere with canonical Histone H3. Various post-translational modifications are important for the proper assembly of CENP-A nucleosomes at the centromeres.
CENP-A plays a crucial role in the assembly of centromeres in vertebrates. It is responsible to localize at the centromere during cell cycle window CENP-A deposition. CENP-A requires activation of the anaphase promoting complex and degradation of CYCLIN A. Plk1 promotes centromere assembly. The CYCLIN B/Cdk1 combination prevents CENPA from binding to HJURP, thereby preventing CENPA from loading at centromeres.
CENP-A controls the centromere identity, function and assembly of nucleosomes at centromere before prophase I arrest. CENP–A also gathers the nucleosomes from the centromere for cell division arrests. The nucleosomes then go to the daughter cells, where segregation continues. The centromere is a special chromosome region that controls cell growth.
The centromere maintenance is accomplished by the MgcRacGAPdependent small GTPase. The MgcRacGAP pathway relies on the diaphanous fomin mDia2. Constitutively active MgcRacGAP is able to rescue the CENPA loading defect in a MgcRacGAP independent cell line.
Complex and overlapping mollic mechanisms govern centromere identification. However, the process governing centromere assembly is fundamental to maintaining genetic stability. Centromeres not only contain DNA sequences, but also contain heritable state that can be propagated independently of the centromeric sequences. The epigenetically controlled assembly of centromeres is shared with gene expression regulation. Scientists are investigating mechanisms that regulate centromere behavior.
PMID: 10806345 by Yeh E.T.H., et al. Ubiquitin-like proteins: new wines in new bottles.
PMID: 10799485 by Kim K.I., et al. A new SUMO-1-specific protease, SUSP1, that is highly expressed in reproductive organs.